Our long range goal is to understand the exceptional role of zinc in oral epithelium. Nutritional zinc deficiency, which inhibits the growth of the y oung rat and most of its organs, has the paradoxical effect of markedly stimulating the activity of the lining epithelium in some regions of the oral cavity, while other regions remain unaffected. We have shown in previous work that stimulated epithelium, similar to precancerous lesions, exhibits higher rates of cell division and increased size and number of cells. We propose here a series of studies on a stimulated region (cheek), an unaffected region (hard palate) and an inhibited region (liver), (1) comparing DNA and RNA per cell and assaying the activity of DNA polymerase at the time when stimulated activity in the cheek is at its height, but body growth has nearly ceased (4 weeks on a zinc-deficient diet). (2) The early death of the zinc-deficient animal precludes prolonged observation of the stimulated regions. We propose to culture explants of cheek and palate mucosa obtained at the height of the stimulated activity in cheek, in order to find out if increased activity has become an inherent feature of the dividing cells. (3) From pilot observations it seems likely that cheek and palate explants will respond differently to excess zinc, lack of zinc and enhancement of zinc uptake from the culture medium. We propose experiments to test these hypothesis.